Infusion Protocol Research Articles

Magnitude and precision of absolute blood volume estimated during hemodialysis

Background: Management of body fluid volumes and adequate prescription of ultrafiltration (UF) remain key issues in the treatment of chronic kidney disease patients.Objective: This study aims to estimate the magnitude as well as the precision of absolute blood volume ( V b ) modeled during regular hemodialysis (HD) using standard data available with modern dialysis machines.Methods: The estimation utilizes a two-compartment fluid model and a mathematical optimization technique to predict UF-induced changes in hematocrit measured by available on-line techniques. The method does not rely on a specific hematocrit sensor or a specific UF or volume infusion protocol and uses modeling and prediction tools to quantify the error in V b estimation.Results: The method was applied to 21 treatments (pre-UF body mass: 65.57 ± 13.44 kg, UF-volume: 3.99 ± 1.14 L) obtained in ten patients (4 female). Pre-HD V b was 5.4 ± 0.53 L with an average coefficient of variation of 9.8% (range 1 to 22%). A significant moderate correlation was obtained when V b was compared to a different method applied to the same data set (r = 0.5). Specific blood volumes remained above the critical level of 65 mL/kg in 17 treatments (80.9%).Conclusion: The method offers the opportunity to detect critical blood volumes during HD and to judge the quality and reliability of that information based on the precision of the V b estimate.

Clinical Outcomes of Using Dexmedetomidine, ProDex and Popfol for Sedation during Mechanical Ventilation in Patients Hospitalized in the Intensive Care Unit: A Triple Blinded Clinical Trial

Background: Sedation plays a crucial role in the care of intensive care unit (ICU) patients, addressing the challenges presented by factors such as agitation, anxiety, and delirium, particularly during mechanical ventilation (MV). Dexmedetomidine and propofol are commonly used sedatives, each with its unique characteristics and side effects. Combining these agents has been proposed to optimize effectiveness and minimize adverse effects. This study aims to compare the efficacy of the dexmedetomidine-propofol combination with dexmedetomidine alone and propofol alone for sedation during mechanical ventilation in ICU patients. Methods: A triple-blinded clinical trial was conducted in Isfahan, Iran, involving patients eligible for spinal fusion surgery and mechanical ventilation. Patients were randomized into three groups: dexmedetomidine alone (DO), propofol alone (PO), and a combination of both drugs (DP) dexmedetomidine-propofol (ProDex). Various dosages and infusion protocols were carefully administered, and patients were assessed for demographic and clinical variables. Hemodynamic parameters and sedation levels were monitored, and statistical analysis was performed. Results: The study involved 87 patients, with the ProDex group demonstrating the shortest mechanical ventilation duration. Hemodynamic stability was observed in the ProDex group, with significantly lower systolic blood pressure and heart rate compared to other groups. Sedation scores did not differ significantly among groups, suggesting similar sedative effects. The ProDex group exhibited favorable outcomes despite differences in hemodynamic variables. Conclusion: The dexmedetomidine-propofol combination appears effective in minimizing side effects associated with monotherapy sedation, leading to favorable clinical outcomes. This study contributes valuable insights into optimizing sedation strategies for mechanically ventilated ICU patients.

Environmental impact analysis of ajmaline challenge protocols: a comparative assessment of carbon footprint reduction in Brugada Syndrome diagnosis

Abstract Background Climate change is an urgent public health crisis that significantly impacts disease development and health outcomes. The 2022 Lancet Countdown Report revealed that healthcare contributes with 5.2% of global emissions, prompting a call for environmentally conscious approaches. In this context, we explored the environmental impact of different ajmaline challenge protocols, aiming to contribute to a more sustainable medical landscape. Purpose This study aims to compare the carbon footprint of two ajmaline challenge protocols commonly used in diagnosing Brugada syndrome, an inherited cardiac disorder associated with sudden cardiac death. Methods We performed a retrospective and observational analysis of adult patients (pts) who underwent ajmaline testing between March 2020 and June 2023 in two hospitals. In Group A (infusion protocol), 1mg/kg of ajmaline diluted in 50 mL of 5% glucose solution was infused in 10 minutes, up to the target dose, until a positive result or termination criteria ensued. In Group B (bolus protocol), 10 mg of ajmaline were administered every 2 minutes, again up to the target dose of 1mg/kg (maximum of 100 mg) or test interruption was indicated. Greenhouse gas emissions resulting from material processing were estimated based on life cycle analyses of each product's composition. Material consumption, waste production, and direct measurement of weights were considered. Results A total of 101 pts were included, 49 pts in group A with a mean age of 47.3±14.3 years old and 52 patients in group B with a mean age of 43.9±16.6 years-old. No complications were observed in either group. Test performance was not evaluated, since both protocols have been previously validated. Group A, utilizing the infusion method, exhibited a higher environmental impact, producing 18.19 kg CO2eq, compared to 6.23 kg CO2eq (p<0.001) in Group B (bolus protocol). Group B not only demonstrated a 66% reduction in CO2eq emissions but also used significantly less plastic (16g vs 102g per test) and glass (1.58 kg vs 1,79Kg), emphasizing its environmental superiority. Conclusions Shifting from infusion to bolus in ajmaline challenge protocols results in a substantial reduction in carbon footprint. Our findings emphasize the potential impact of adopting more dematerialized approaches in cardiac testing, urging healthcare professionals to embrace sustainable practices. Despite the study's limited sample size, the global adoption of such environmentally friendly strategies promises significant positive effects on healthcare's environmental footprint.

Contrast Enhancement in Breast Cancer: Magnetic Resonance vs. Mammography: A 10-Year Systematic Review.

Contrast Enhancement Magnetic Resonance (CEMR) and Contrast-Enhanced Mammography (CEM) are important diagnostic tools to evaluate breast cancer patients, and both are objects of interest in the literature. The purpose of this systematic review was to select publications from the last ten years in order to evaluate the literature contributions related to the frequency of contrast agents used, administration techniques and the presence of adverse reactions. We have selected, according to the PRISMA statement, publications reviewed on Pub Med in the period from 1 January 2012 to 31 December 2022. The search engine was activated using the following keywords: "CESM", "CEM", "CEDM", "Contrast mammography" for CEM, "DCE-MRI", "Contrast Enhancement MRI" for CEMR, excluding reviews, book chapters and meta-analyses. From the total number of publications, we made a preliminary selection based on titles and abstracts and excluded all articles published in languages other than English and all experimental studies performed on surgical specimen or animal population, as well as all articles for which the extended version was not available. Two readers evaluated all the articles and compiled a pre-compiled form accordingly. After a preliminary collection of 571 CEM publications, 118 articles were selected, relating to an overall population of 21,178 patients. From a total of 3063 CEMR publications, 356 articles relating to an overall population of 45,649 patients were selected. The most used contrast agents are Iohexol for CEM (39.83%) and Gadopentetic acid (Gd-DTPA) for CEMR (32.5%). Regarding the CEM contrast administration protocol, in 84.7% of cases a dose of 1.5 mL/kg was used with an infusion rate of 2-3 mL/s. Regarding the CEMR infusion protocol, in 71% of cases a dose of 1 mmol/kg was used at an infusion rate of 2-4 mL/s. Twelve out of 118 CEM articles reported allergic reactions, involving 29 patients (0.13%). In DCE-MRI, only one out of 356 articles reported allergic reactions, involving two patients (0.004%). No severe reactions were observed in either cohort of exams. CEM and CEMR are essential contrast methods to evaluate breast diseases. However, from the literature analysis, although there are preferences on the uses of the contrast agent (Iohexol for CESM, G-DTPA for CEMR), a wide range of molecules are still used in contrast methods, with different administration protocols. Based on the collected data, it is possible to state that both methods are safe, and no severe reactions were observed in our evaluation.

Late Treatment With Autologous Expanded Regulatory T-cell Therapy After Alemtuzumab Induction Is Safe and Facilitates Immunosuppression Minimization in Living Donor Renal Transplantation.

The TWO Study (Transplantation Without Overimmunosuppression) aimed to investigate a novel approach to regulatory T-cell (Treg) therapy in renal transplant patients, using a delayed infusion protocol at 6 mo posttransplant to promote a Treg-skewed lymphocyte repopulation after alemtuzumab induction. We hypothesized that this would allow safe weaning of immunosuppression to tacrolimus alone. The COVID-19 pandemic led to the suspension of alemtuzumab use, and therefore, we report the unique cohort of 7 patients who underwent the original randomized controlled trial protocol. This study presents a unique insight into Treg therapy combined with alemtuzumab and is therefore an important proof of concept for studies in other diseases that are considering lymphodepletion. Living donor kidney transplant recipients were randomized to receive autologous polyclonal Treg at week 26 posttransplantation, coupled with weaning doses of tacrolimus, (Treg therapy arm) or standard immunosuppression alone (tacrolimus and mycophenolate mofetil). Primary outcomes were patient survival and rejection-free survival. Successful cell manufacturing and cryopreservation until the 6-mo infusion were achieved. Patient and transplant survival was 100%. Acute rejection-free survival was 100% in the Treg-treated group at 18 mo after transplantation. Although alemtuzumab caused a profound depletion of all lymphocytes, including Treg, after cell therapy infusion, there was a transient increase in peripheral Treg numbers. The study establishes that delayed autologous Treg therapy is both feasible and safe, even 12 mo after cell production. The findings present a new treatment protocol for Treg therapy, potentially expanding its applications to other indications.

On the analysis of functional PET (fPET)-FDG: baseline mischaracterization can introduce artifactual metabolic (de)activations.

Functional Positron Emission Tomography (fPET) with (bolus plus) constant infusion of [18F]-fluorodeoxyglucose FDG), known as fPET-FDG, is a recently introduced technique in human neuroimaging, enabling the detection of dynamic glucose metabolism changes within a single scan. However, the statistical analysis of fPET-FDG data remains challenging because its signal and noise characteristics differ from both classic bolus-administration FDG PET and from functional Magnetic Resonance Imaging (fMRI), which together compose the primary sources of inspiration for analytical methods used by fPET-FDG researchers. In this study, we present an investigate of how inaccuracies in modeling baseline FDG uptake can introduce artifactual patterns to detrended TAC residuals, potentially introducing spurious (de)activations to general linear model (GLM) analyses. By combining simulations and empirical data from both constant infusion and bolus-plus-constant infusion protocols, we evaluate the effects of various baseline modeling methods, including polynomial detrending, regression against the global mean time-activity curve, and two analytical methods based on tissue compartment model kinetics. Our findings indicate that improper baseline removal can introduce statistically significant artifactual effects, although these effects characterized in this study (~2-8%) are generally smaller than those reported by previous literature employing robust sensory stimulation (~10-30%). We discuss potential strategies to mitigate this issue, including informed baseline modeling, optimized tracer administration protocols, and careful experimental design. These insights aim to enhance the reliability of fPET-FDG in capturing true metabolic dynamics in neuroimaging research.

7137 The Sugar Saga: A Profound Case Of Diabetic Ketoacidosis Due To Enfortumab Vedotin

Abstract Disclosure: P. Aron: None. B. Connell: None. R. Longo: None. J. Upadhyay: None. This is a case of severe hyperglycemia with the use of Enfortumab Vedotin (EV) in the setting of advanced urothelial cancer. EV is a nectin-4-directed antibody-drug conjugate with a microtubule inhibitor approved for treating advanced/recurrent disease. It is the first of its class that is an antibody-drug conjugate (ADC), targeting nectin, but not the first ADC to cause hyperglycemia. Here we present a case of severe insulin resistance requiring insulin infusion at 50 units/hour in addition to subcutaneous insulin all in the setting of EV use.74 year old male with BMI of 28 and HbA1c of 7.5%, managed only with diet was started on EV for metastatic urothelial cancer. Patient received one cycle (3 doses) of EV (on days 1, 8, 15) and thereafter noticed worsening of hyperglycemia with blood glucose of 533 mg/dL, requiring subcutaneous insulin. Patient’s blood glucose readings remained elevated and he was admitted to the hospital as he was found to be in DKA with a pH of 7.2, bicarbonate 14 mmol/L, anion gap of 16 mmol/L and a glucose of 558 mg/dL. The patient was started on intravenous insulin (IV) infusion using insulin infusion protocol titrated up to 14 units an hour with an additional 30 units of glargine. Patients’ clinical condition continued to worsen and he was in septic shock with pressors and on insulin infusion exceeding 55 units/hour, NPH at 50 units, and regular insulin 30 units with glucose persistently above 400 mg/dL. Patient was started on hydrocortisone 50mg every 6h and his blood glucose readings eventually normalized over a span of 1 week. Patient eventually was able to be discharged to rehabilitation with just a correctional humalog insulin. Our case demonstrates DKA as a consequence of severe insulin resistance seen as a side effect of EV. Hyperglycemia is seen in 8% of patients using this medication, but severe cases are mostly seen with high BMI and uncontrolled diabetes. This case illustrates the fact that one needs to be cautious in ALL patients with diabetes when using this drug and warrants screening for DKA/severe insulin resistance if blood glucose is running >250mg/dL. The exact mechanism for hyperglycemia is unknown but it is likely immunomodulatory and therefore treatment with pulse dose steroids may help with overcoming insulin resistance in this setting like in our patient. More research needs to be done to understand mechanisms and establish treatment guidelines for severe insulin resistance and hyperglycemia caused by this medication. Presentation: 6/1/2024

Prolonged magnesium sulfate infusion as adjuvant analgesia in postoperative transplant patients in the pediatric ICU: Preliminary results of a feasibility study.

The opioid crisis has emphasized identification of opioid-sparing analgesics. This study was designed as a prospective trial with retrospective control group to determine feasibility for implementing a high-dose prolonged magnesium sulfate infusion for adjuvant analgesia in the pediatric intensive care unit. Approval was granted for study of children receiving total pancreatectomy with islet cell autotransplantation and liver transplantation ages 3-18 years. Study exclusions were pregnancy, neuromuscular disease, hypersensitivity, preoperative creatinine >1.5 times upper limit normal, arrhythmia or pacemaker presence, and clinician concern. Eleven patients were enrolled between January 2020 and December 2022. Magnesium sulfate bolus (50 mg/kg) followed by intravenous infusion (15 mg/kg/h) was initiated in the operating room and extended postoperatively (maximum 48 h). Serum magnesium levels were monitored serially. To prioritize safety, infusion dose was decreased by 5 mg/kg/h for levels greater than 3.5 mg/dL. Clinical team otherwise followed standard multimodal pain practice. Primary outcome was oral morphine equivalent per kg per day during intensive care course (maximum 7 days). Secondary outcomes focused primarily on magnesium safety, including hemodynamic variables, electrolyte variables, respiratory support, and opioid-related side effects. There were no serious adverse events. Treatment group trended toward slightly higher intravenous fluid requirement (~1 bolus), however no increase in blood product. Treatment and control groups were otherwise comparable in targeted outcomes and overall adverse event profile. Use of a high-dose magnesium sulfate infusion protocol for analgesic postoperative use in select transplant recipients appears feasible for continued optimization of study in the PICU.

In-use stability of Rituximab and IVIG during intravenous infusion: Impact of peristaltic pump, IV bags, flow rate, and plastic syringes

This study investigates the impact of intravenous (IV) infusion protocols on the stability of Intravenous Immunoglobulin G (IVIG) and Rituximab, with a particular focus on subvisible particle generation. Infusion set based on peristaltic movement (Medifusion DI-2000 pump) was compared to a gravity-based infusion system (Accu-Drip) at different flow rates. The impacts of different diluents (0.9 % saline and 5.0 % dextrose) and plastic syringes with or without silicone oil (SO) were also investigated. The results from the aforementioned particular case demonstrated that peristaltic pumps generated high levels of subvisible particles (prominently < 25 µm), exacerbated by increasing flow rates, specifically in formulations lacking surfactants. Other factors, such as diluent type and syringe composition, also increased the number of subvisible particles. Strategies that can help overcome these complications include surfactant addition as well as the use of SO-free syringes and a gravity infusion system, which aid in reducing particle formation and preserving antibody monomer during administration. Altogether, these findings highlight the importance of the careful selection of formulations and infusion protocols to minimize particle generation during IV infusion both for patients’ safety and treatment efficacy.

Comparative safety and efficacy of a hybrid intravenous and oral diltiazem protocol for acute rate control in the emergency department

Study objectiveIntravenous diltiazem has experienced numerous supply shortages over the past few years. The purpose of this study was to compare the safety and efficacy of a traditional diltiazem intravenous bolus and continuous infusion protocol to a diltiazem intravenous bolus and oral maintenance protocol for acute rate control in the emergency department. MethodsPatients who received intravenous diltiazem in the emergency department between January 1, 2018 and May 31, 2019 were screened. Patients were included if they received the diltiazem intravenous bolus and continuous infusion protocol (IV + infusion group) or the hybrid diltiazem intravenous bolus and oral maintenance protocol (IV + PO group). The primary outcome was the proportion of patients with rate control, without need for additional rate control agents or additional boluses during the maintenance phase. ResultsA total of 106 patients were matched with 53 patients in each group. For the primary outcome of rate control at four hours, 62.3% of patients in the intravenous bolus + infusion group versus 75.5% of patients in the IV bolus + PO group (p = 0.142) achieved rate control. There was no difference in rates of hypotension or bradycardia between groups. ConclusionResults of this study demonstrated no difference in acute rate control when using a hybrid IV and oral diltiazem protocol, compared to a traditional IV bolus and infusion strategy. This information supports the further use of a hybrid diltiazem IV and oral protocol, which provides increased flexibility during shortages of either medication.

A Modified Floxuridine Reduced-Dose Protocol for Patients with Unresectable Colorectal Liver Metastases Treated with Hepatic Arterial Infusion.

Most patients treated with the standard dosing protocol (SDP) of hepatic arterial infusion (HAI) floxuridine require dose holds and reductions, thereby limiting their HAI therapy. We hypothesized that a modified dosing protocol (MDP) with a reduced floxuridine starting dose would decrease dose holds, dose reductions, and have similar potential to convert patients with unresectable colorectal liver metastases (uCRLM) to resection. We reviewed our institutional database of patients with uCRLM treated with HAI between 2016 and 2022. In 2019, we modified the floxuridine starting dose to 50% (0.06 mg/kg) of the SDP (0.12 mg/kg). We compared treatment related outcomes between the SDP and MDP cohorts. Of n = 33 patients, 15 (45%) were treated on the SDP and 18 (55%) with our new institutional MDP. The MDP cohort completed more cycles before a dose reduction (mean 4.2 vs. 2), received more overall cycles (median 7.5 vs. 5), and averaged 39 more days of treatment (all P < 0.05). The SDP experienced more dose reductions (1.4 vs. 0.61) and dose holds (1.2 vs. 0.2; both P < 0.01). Of the patients in each group potentially convertible to hepatic resection, three patients (23%) in the SDP and six patients (35%) in the MDP group converted to resection (P = 0.691). Overall, four patients (27%) in the SDP developed treatment ending biliary toxicity compared with one patient (6%) in the MDP. A 50% starting dose of HAI floxuridine provides fewer treatment disruptions, more consecutive floxuridine cycles, and a similar potential to convert patients with initially uCRLM for disease clearance.

Improving Compliance with a Nurse-Driven Protocol for Unfractionated Heparin Infusions in Patients with Venous Thromboembolism.

Unfractionated heparin (UFH) is a high-risk medication that can cause bleeding and/or thrombotic complications if not managed appropriately. Between January and July 2019, our institution experienced a high number of patient safety events related to UFH infusion for the treatment of venous thromboembolism (VTE). The aim of this quality improvement (QI) initiative was to prevent these safety events by improving compliance with our institution's nurse-driven VTE UFH infusion protocol. Baseline data for patients on the VTE UFH protocol were collected to identify improvement opportunities. Compliance with eight standards of care related to the VTE UFH infusion protocol was measured. Time to first therapeutic activated partial thromboplastin time (aPTT) was recorded to assess the benefit of improved compliance. Institutional policy updates were made to clarify the management of UFH infusions and documentation in the electronic health record. A multidisciplinary workgroup implemented order set changes, nursing communication orders, UFH infusion reports, and a nursing education module to promote compliance with the protocol. The overall rate of compliance with the VTE UFH infusion protocol increased from 79.4% at baseline to 85.2% following implementation of the QI initiative, and the median time to first therapeutic aPTT decreased from 831.5 minutes to 808 minutes over the same period. A multidisciplinary initiative to address improvement opportunities in a nurse-driven UFH protocol for VTE treatment increased compliance with the protocol and decreased the time to first therapeutic aPTT.

#2956 Hemodynamic evaluation of different replacement fluids during therapeutic plasmapheresis with Crit-line™

Abstract Background and Aims Therapeutic plasmapheresis (TP) is an extracorporeal technique used to remove pathogenic macromolecules from the plasma. Human serum Albumin (HSA) or fresh frozen plasma can be used as replacement fluid, alone or in combination, and with or without the addition of a crystalloid such as saline. There is wide practice variation in the type of replacement fluid and according the procedure of TP such as single plasma exchange (SPE) or double plasmafiltration (DFPP). Replacing plasma with crystalloid carries a risk of hypotension if the proportion of replacement with crystalloid exceeds 30%. CRIT-LINE™ monitor estimate RBV changes during HD based on measurements of hematocrit and could be used in hemodialysis to prevent hypotensive episodes. Method We conducted a retrospective case series study in a tertiary center to evaluate RBV changes during TP (SPE &amp; DFPP) in three patients with PIDC treated with chronic TP using SPE or DFPP according to guidelines. For each patient and procedure (SPE or DFPP) we compare different substitution fluid infusion protocol between 2021 and 2023. We evaluated each patient's sessions with CRITLINE™ continuous RBV monitoring during either SPE or DFPP with comparison of different replacement fluid protocols. For DFPP with plasmafractionator EC30 (Asahi Kasei Medical Co., Japan) or medopen30 (Infomed, Switzerland), we compare protocols as follows (1) continuous infusion of 500 ml of HSA 4% throughout the session and (2) 500 ml HSA 4% at the last 20 min of the session. For SPE, we compare protocols as follows (1) 100% volume of HSA 4% supplementation (2) a combination of 70% HSA 4% and 30% of saline started at the last part of the session (3) a combination of 70% HSA 4% and 30% of saline started at the first part of the of the session. Results BVM decreased by 15% ± 5% in DFPP session with 500 ml HSA 4% at the last 20 min of the session and by 12% ± 3 in DFPP session with continuous infusion of 500 ml of HSA 4% throughout the session . In SPE, BVM decreased by 18% ± 2 in session with a combination of 70% HSA 4% and 30% of saline and by 10% in session with 100% albumin substitution. Hypotensive episodes occurred in session with a combination of 70% albumin 4% and 30% of saline at the end of session. Conclusion CRITLINE IV continuous RBV monitoring is an interesting tool that can be used to evaluate the optimal substitution fluid in TP and for prevention of hypotension. Randomized control trial are needed to confirm the results.

Implementation of an Accelerated Infusion Protocol (90-Minute Infusion) of Rituximab and Its Safety in Patients With Autoimmune Rheumatic Diseases at a Tertiary Veterans Affairs Center.

Background Rituximab, a chimeric monoclonal antibody targeting the CD20 protein on the surface of B cells, is used to treat several rheumatologic and oncologic diseases. The standard infusion duration of rituximab is four hours. Objective Evaluating the safety of administering the accelerated 90-minute protocol at our Veterans Affairs center to patients with rheumatologic diseases and monitoring for any infusion-related reactions. This study is unique as it examines infusion rates faster than those most described (120 minutes). Methods Patients treated with rituximab for autoimmune diseases between June 2020 and June 2022 at our center were included in the study. Our patients were over 18 years of age,met the inclusion criteria, and had received previous rituximab infusions without prior infusion-related reactions. They received the accelerated protocol of 90 minutes over their next cycles and were monitored for any reactions during their infusions. Results A total of 34 patients receiving 76 infusions were included in the analysis. Most of the patients were males (n = 27). The most prevalent indication for rituximab infusion was rheumatoid arthritis (n = 20).Out of 76 infusions, only two infusion-related reactions were recorded (2.6% incidence). The first patient had itching and a sore throat, indicating a grade 1A reaction. The second patient developed chest pain and dyspnea, which resolved with diphenhydramine and albuterol. For both, the infusion was completed after appropriate management. Conclusion The incidence of infusion-related reactions during the accelerated 90-minute rituximab infusion was remarkably low and well-tolerated by our rituximab-experienced patients. Only two infusions were complicated by a reaction, an incidence comparable to or even lower than other reported 120-minute infusion protocols.This protocol is time- and cost-efficient, allowing for more infusions per chair per day at our center.

The patterns in urine excretion and transvascular fluid exchange in human subjects during intravenous fluid infusion: A quantitative analysis.

Investigations of responses of animals and humans to changes of plasma volume are usually reported as average responses of groups of individuals. This ignores considerable quantitative variation between individuals. We examined the hypothesis that individual responses follow a common temporal pattern with variations reflecting different parameters describing that pattern. We illustrate this approach using data of Hahn, Lindahl and Drobin (Acta Anaesthesiol Scand.2011, 55:987-94) who measured urine volume and haemoglobin dilution of 10 female subjects during intravenous Ringer infusions for 30 min and subsequent 3.5 h. The published time courses were digitised and analysed to determine if a family of mathematical functions accounted for the variation in individual responses. Urine excretion was characterised by a time delay (Td) before urine flow increased and a time course of cumulative urine excretion described by a logarithmic function. This logarithmic relation forms the theoretical basis of a family of linear relations describing urine excretion as a function of Td. Measurement of Td enables estimation of subsequent values of urine excretion and thereby the fraction of infused fluid retained in the body. The approach might be useful for physiologists and clinical investigators to compare the response to infusion protocols when both test and control responses can be described by linear relations between cumulative urine volume at specific times and Td. The approach may also be useful for clinicians by complementing strategies to guide fluid therapy by enabling the later responses of an individual to be predicted from their earlier response.

Desensitizing the autonomic nervous system to mitigate anti-GD2 monoclonal antibody side effects.

Anti-GD2 monoclonal antibodies (mAbs) have shown to improve the overall survival of patients with high-risk neuroblastoma (HR-NB). Serious adverse events (AEs), including pain, within hours of antibody infusion, have limited the development of these therapies. In this study, we provide evidence of Autonomic Nervous System (ANS) activation as the mechanism to explain the main side effects of anti-GD2 mAbs. Through confocal microscopy and computational super-resolution microscopy experiments we explored GD2 expression in postnatal nerves of infants. In patients we assessed the ANS using the Sympathetic Skin Response (SSR) test. To exploit tachyphylaxis, a novel infusion protocol (the Step-Up) was mathematically modelled and tested. Through confocal microscopy, GD2 expression is clearly visible in the perineurium surrounding the nuclei of nerve cells. By computational super-resolution microscopy experiments we showed the selective expression of GD2 on the cell membranes of human Schwann cells in peripheral nerves (PNs) significantly lower than on NB. In patients, changes in the SSR were observed 4 minutes into the anti-GD2 mAb naxitamab infusion. SSR latency quickly shortened followed by gradual decrease in the amplitude before disappearance. SSR response did not recover for 24 hours consistent with tachyphylaxis and absence of side effects in the clinic. The Step-Up protocol dissociated on-target off-tumor side effects while maintaining serum drug exposure. We provide first evidence of the ANS as the principal non-tumor target of anti-GD2 mAbs in humans. We describe the development and modeling of the Step-Up protocol exploiting the tachyphylaxis phenomenon we demonstrate in patients using the SSR test.

Implementation of perioperative blood glucose monitoring and insulin infusion protocol can decrease postoperative infection rate in diabetic patients undergoing elective craniotomy: An observational study

BackgroundSevere perioperative hyperglycemia (SH) is a proven risk factor for postoperative complications after craniotomy. To reduce this risk, it has been proposed to implement the standardized clinical protocol for scheduled perioperative blood glucose concentration (BGC) monitoring. This would be followed by intravenous (IV) insulin infusion to keep BGC below 180 mg/dl in the perioperative period. The aim of this prospective observational study was to assess the impact of this type of protocol on the postoperative infection rate in patients undergoing elective craniotomy. MethodsA total of 42 patients were prospectively enrolled in the study. Protocol included scheduled BGC monitoring in the perioperative period and rapid-acting insulin IV infusion when intraoperative SH was detected. The diagnosis of infection (wound, pulmonary, blood stream, urinary tract infection or central nervous system infection) was established according to CDC criteria within the first postoperative week. A previously enrolled group of patients with sporadic BGC monitoring and subcutaneous insulin injections for SH management was used as a control group. ResultsAn infectious complication (i.e., pneumonia) was diagnosed only in one patient (2 %) in the prospective group. In comparison with the control group, a decrease in the risk of postoperative infection was statistically significant with OR = 0.08 [0.009 – 0.72] (p = 0.02). Implementation of the perioperative BGC monitoring and the correction protocol prevented both severe hyperglycemia and hypoglycemia with BGC < 70 mg/dl. ConclusionScheduled BGC monitoring and the use of low-dose insulin infusion protocol can decrease the postoperative infection rate in patients undergoing elective craniotomy. Future studies are needed to prove the causality of the implementation of such a protocol with an improved outcome.

Intravenous Iron Supplementation in Pregnancy: A Quality Improvement Project on Maternal Transfusion Reduction [ID 2683469

INTRODUCTION: Intravenous (IV) iron supplementation for patients with iron deficiency anemia in pregnancy has been shown to improve hemoglobin (Hb) levels in the peripartum period and ultimately lead to a decrease in severe maternal morbidity (SMM), specifically blood transfusion. The objective of this study was to analyze the effects of IV iron supplementation on maternal pre-delivery Hb levels after the implementation of an institution-based protocol focused on maternal red blood cell transfusion reduction. METHODS: We performed a retrospective review of patients who received IVFe supplementation after the implementation of a maternal transfusion reduction bundle at our Level IV maternal care center in 2020. We reviewed changes in maternal Hb pre-infusion and pre-delivery over a 3-year period (2020–2023), along with rates of postpartum blood transfusion. Patients were excluded if they received an antepartum blood transfusion. Maternal demographics, ferritin and Hg levels were compared between the two groups using GraphPad Prism software. RESULTS: Two hundred ninety-five patients met inclusion criteria; most patients were Hispanic (71.9%), had Medicaid (51.9%), and underwent a vaginal delivery (76.9%). Mean gestational age at time of infusion was 34.2 weeks (95% CI, 33.7–34.7) The average Hb pre-infusion and pre-delivery were 8.9 (95% CI, 8.8–9.0) and 10.6 (95% CI, 10.4–10.8), respectively. The change in maternal Hb at time of delivery increased by 2 points (P&lt;.0001). Only two patients received a blood transfusion postpartum. CONCLUSION: Implementation of a standardized antenatal IV iron infusion protocol can improve maternal pre-delivery Hb levels and reduce morbidity associated with blood transfusion.

Noniatrogenic hypoglycemia: A universal marker for poor outcomes

ObjectivePrevious retrospective studies have established a relationship between postoperative hypoglycemia and adverse outcomes after cardiac surgery, but none have accounted for the cause of hypoglycemia. MethodsA retrospective review was performed of patients who underwent cardiac surgery at a single institution between 2016 and 2021. Patients were categorized as hypoglycemic if they had 1 or more postoperative blood glucose measurement less than 70 mg/dL and normoglycemic otherwise. Hypoglycemia was subcategorized as noniatrogenic (underlying liver failure, adrenal insufficiency, sepsis, or shock) or iatrogenic (insulin infusion continued while nil per os or infusion protocol violated) via manual chart review. Baseline characteristics were compared between groups using Pearson χ2, analysis of variance, and Kruskal-Wallis testing, and outcomes were compared using multivariable logistic regression. ResultsIn total, 5373 patients and 183,346 glucose measurements were included. Hypoglycemia occurred in 5% (267) of patients, of whom 63% (169) were iatrogenic and 37% (98) were noniatrogenic. In a multivariate analysis adjusting for age, sex, case urgency, pre-existing diabetes, and bypass time, both iatrogenic and noniatrogenic hypoglycemia were associated with greater odds of renal failure, prolonged ventilation, and prolonged intensive care unit length of stay relative to normoglycemia, but the magnitude was substantially lower in iatrogenic hypoglycemia. Patients with noniatrogenic hypoglycemia had 68.6 times greater odds of mortality relative to patients who were normoglycemic (odds ratio, 68.6; confidence interval, 39.5-119), but patients with iatrogenic hypoglycemia had no increased odds of mortality (odds ratio, 1.45; confidence interval, 0.77-2.73). ConclusionsWhen excluding patients with conditions known to cause hypoglycemia from the analysis, the morbidity and mortality of iatrogenic hypoglycemia from tight postoperative glycemic control is dramatically attenuated.

The Practice of Prolonging Meropenem Infusion: A Narrative Review of Literatures Over the Last Decade

Background: The emergence of Antimicrobial Resistance (AMR) has forced clinicians and medical professionals to implement a strict Antimicrobial Stewardship policy. One of the pillar of Antimicrobial Stewardship is by optimizing the use of antibiotic agents. Beta-lactams demonstrate a time-dependent effect in combating bacteria. Since it is pharmacodynamically supported, a prolonged exposure via intravenous administration could be a feasible strategy to maximize the bactericidal effect. Meropenem, a beta-lactam antibiotic of carbapenems sub-class, also falls into the category above. However, there are questions to be answered regarding its stability, compatibility, safety, and clinical outcomes superiority compared to the standard intermittent infusion, before we can determine its effectiveness to be delivered as prolonged or extended infusion. Aims: This article would like to review literatures regarding the rationale behind the practice of prolonging meropenem infusion from the last decade. Method: For this narrative review we utilized articles extracted from Cochrane Library, ScienceDirect, and SageJournals databases from the last ten years. We also added complementary related articles from UpToDate®. Selected articles were limited to those published in english. Inclusion criteria specifically only including related articles to the practice of prolonging meropenem infusion on adult patients. A total of 18 articles were reviewed for the synthesis of this narrative review. Conclusion: Meropenem is eligible for prolonged infusion protocol since it is theoretically supported, adequate in stability, less concern for incompatibility, and potentially can provide better clinical outcomes compared to standard intermittent infusion.